Dissertation / PhD Thesis

FZJ-2013-04358

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Stereoselective synthesis of vicinal diols with enzymatic cascade reactions

Kulig, J. (Corresponding author)FZJ*

2013
Forschungszentrum Jülich GmbH Zentralbibliothek, Verlag Jülich
ISBN: 978-3-89336-911-9

Please use a persistent id in citations: http://hdl.handle.net/2128/5409

Abstract: Alcohol dehydrogenases are of high interest for the stereoselective synthesis of building blocks with multi-chiral centres. They are implemented for single enzymatic reduction or oxidation steps or be part of synthetic enzymatic multi-step cascades for the production of industrially relevant chiral synthons. Although biotransformations with alcohol dehydrogenases are widespread, enzymes, which accept sterically demanding substrates, especially α-hydroxy ketones, are not common in nature. Therefore chemical methods for the synthesis of chiral 1,2-diols are still first choice. As a drawback, alcohol dehydrogenases require expensive nicotinamide cofactors such as NAD(H) or NADP(H) for their activity. Prices of these cofactors prevent their application in stoichiometric amounts and therefore regeneration of nicotinamide cofactors is an essential issue for biotechnological purposes. Therefore a co-substrate is required that is transformed to the respective co-product in equimolar amounts relative to the product. This co-product has to be separated from the product or must be removed $\textit{in situ}$, which decreases atom- and process economy. In this work the carboligation of two inexpensive aldehydes catalysed by ThDPdependent enzymes is combined with a subsequent reduction of the intermediately formed α-hydroxy ketone by alcohol dehydrogenases. Therefore, a suitable cofactor regeneration system with smart $\textit{in situ}$ co-product removal had to be developed in order to gain high eco-efficiency of the synthetic enzyme cascade. To achieve the aim, the following work packages were addressed: 1. Investigation of the substrate range of eight available alcohol dehydrogenases with focus on reduction of bulky-bulky α-hydroxy ketones; 2. Determination of the stereoselectivity of the first and the second step of the synthetic cascade; 3. Selection of the most promising enzyme(s) for the reduction of α-hydroxy ketones (which turned out to be the alcohol dehydrogenase from $\textit{Ralstonia}$ sp.) and its detailed biochemical characterisation with focus on the reduction of α-hydroxy ketones; 4. Evaluation of a suitable cofactor regeneration system (substrate-coupled and enzyme-coupled approach) for the enzymatic 2-step synthesis, where smart [...]

Keyword(s): Dissertation

Note: Universität Düsseldorf, Diss., 2013

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Contributing Institute(s):

1. Biotechnologie (IBG-1)

Research Program(s):

1. 899 - ohne Topic (POF2-899) (POF2-899)

Appears in the scientific report 2013

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Database coverage:

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